Brief Biography:

Professional Experience

2017-present Professor, Principal Investigator, Shanghai Institute of Nutrition and Health (SINH), CAS

2013-2016 Professor, Principal Investigator, Institute for Nutritional Sciences, Shanghai Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China

2009-2012 Postdoctoral Fellow, Boston University Medical School, Boston, MA, USA

2004-2008 Teaching Assistant, Department of Molecular and Cellular Biology, University of Guelph, Guelph, Canada

Education

2004-2008 Ph.D. (Molecular and Cellular Biology) University of Guelph, Guelph, Ontario, Canada

2000-2003 M.S. (Fermentation) Tianjin University of Science and Technology, Tianjin, China

1996-2000 B.S. (Biological Engineering) Tianjin University of Science and Technology, Tianjin, China

Research Areas:

Background
Changes in human behavior and lifestyle have caused markedly increased risk of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), which magnify the risk of cardiovascular morbidity and mortality. Type 2 diabetes is a long term metabolic disorder that is characterized by hyperglycemia and insulin resistance, whereas NAFLD is characterized by increased fat and inflammation in the liver, which may progress to the end-stage liver disease, such as cirrhosis, and liver cancer. The liver is one of the major metabolic organs, and is essential for the regulation of whole-body glucose and lipid homeostasis. Impairment of liver function is an early hallmark of obesity-associated metabolic disorders, such as insulin resistance and type 2 diabetes. Therefore, the unravelling of pathophysiological mechanisms of the liver is of critical for the prevention and treatment of metabolic diseases.

Major research interests
The research interest of Li laboratory is to study pathophysiological mechanisms of metabolic diseases. We are currently focused on identifying novel metabolic regulators of signal transduction pathways in metabolic tissues including liver and adipose tissue. We have a major research effort in the study of molecular mechanisms that regulate lipid, glucose and energy metabolism at the transcriptional and post-translational levels. We aim to dissect these biological processes by employing a variety of molecular and cellular approaches, and animal models including both genetically modified (transgenic and knockout) and diet-induced mouse models. The ultimate goal of this integrated approach is to unravel potential therapeutic targets of metabolic pathways for treating metabolic syndrome, such as fatty liver disease, hyperglycemia, hyperlipidemia, obesity, insulin resistance and type 2 diabetes.

1. Hepatic Insulin Resistance and Type 2 Diabetes.
Insulin resistance plays essential roles in the development of type 2 diabetes. The understanding of the underlying mechanism of insulin resistance is of importance for designing therapeutic approaches for the treatment of hyperglycemia and type 2 diabetes.

2. Deregulation of Lipid Metabolism and NAFLD.
Aberrant fatty acid metabolism plays important roles in the development of hepatic steatosis. Hepatic fatty acid oxidation and the subsequent production of ketone bodies are one of the central processes in hepatic lipid metabolism. The inability of fatty acid to be adequately oxidized causes aberrant accumulation of triglyceride in the liver, and results in the development of hepatic steatosis or nonalcoholic fatty liver disease. Hepatic steatosis is the most common and potentially serious metabolic diseases, which can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and liver cancer.

3. Molecular Control of Metabolism and Nonalcoholic Steatohepatitis (NASH).
NASH is a syndrome that develops in patients of liver inflammation and damage, which are caused by excessive fat deposition in the liver. NASH can progress to cirrhosis and liver cancer. NASH is strongly associated with metabolic diseases, including obesity, dyslipidemia, and insulin resistance. Given that no FDA approved drug is available, there is an urging need for the development of therapeutic approaches for the treatment of NASH.

Selected Publications: (*Corresponding Author)

1. Cui A^#, Xue Y^#, Su W^#, Lin J, Liu Y, Cai G, Wan Q, Jiang Y, Ding D, Zheng Z, Wei S, Li W, Shen J, Wen J, Huang M, Zhao J, Zhang X, Zhao Y, Li H, Ying H, Zhang H, Bi Y, Chen Y, Xu A, Xu Y*, Li Y*. Glucose regulation of adipose tissue browning by CBP/p300 and HDAC3-mediated reversible acetylation of CREBZF. Proc Natl Acad Sci U S A 2024;121(16):e2318935121
2. Liu Y^#, Su W^#, Liu Z^#, Hu Z, Shen J, Zheng Z, Ding D, Huang W, Li W, Cai G, Wei S, Li N, Fang X, Li H, Qin J, Zhang H, Xiao Y, Bi Y, Cui A*, Zhang C*, Li Y*. Macrophage CREBZF orchestrates inflammatory response to potentiate insulin resistance and type 2 diabetes. Advanced Science 2024;e2306685
3. Xue Y^#, Cui A^#, Wei S, Ma F, Liu Z, Fang X, Huo S, Sun X, Li W, Hu Z, Liu Y, Cai G, Su W, Zhao J, Yan X, Gao C, Wen J, Zhang H, Li H, Liu Y, Lin X, Xu Y, Fu W*, Fang J*, Li Y*. Proline hydroxylation of CREB-regulated transcriptional coactivator 2 controls hepatic glucose metabolism. Proc Natl Acad Sci U S A 2023;120(23):e2219419120
4. Ma F, Liu Y, Hu Z, Xue Y, Liu Z, Cai G, Su W, Zheng Z, Fang Z, Yan X, Ding D, Sun X, Jiang Y, Wei S, Li W, Zhao J, Zhang H, Li H, Xiao D, Zhang C, Ying H, Qin J, Gao X, Dai X, Fu W, Xu Y*, Li Y*, Cui A*. Intrahepatic osteopontin signaling by CREBZF defines a checkpoint for steatosis-to-NASH progression. Hepatology 2023;78(5):1492-1505
5. Cui A^#, Li J^#, Ji S^#, Ma F, Wang G, Xue Y, Liu Z, Gao J, Han J, Tai P, Wang T, Chen J, Ma X*, Li Y*. The effects of B1344, a novel fibroblast growth factor 21 analog, on nonalcoholic steatohepatitis in nonhuman primates. Diabetes 2020;69(8):1611-1623
6. Hu Z^#, Han Y^#, Liu Y, Zhao Z, Ma F, Cui A, Zhang F, Liu Z, Xue Y, Bai J, Wu H, Bian H, Chin YE, Yu Y, Meng Z, Wang H, Liu Y, Fan J, Gao X, Chen Y, Li Y*. CREBZF as a key regulator of STAT3 pathway in the control of liver regeneration in mice. Hepatology 2020;71(4):1421-1436
7. Wu R, Dang F, Li P, Wang P, Xu Q, Liu Z, Li Y, Wu Y, Chen Y, Liu Y*. The circadian protein Period2 suppresses mTORC1 activity via recruiting TSC1 to mTORC1 complex. Cell Metabolism 2019;29(3):653-667
8. Han Y^#, Hu Z^#, Cui A, Liu Z, Ma F, Xue Y, Liu Y, Zhang F, Zhao Z, Yu Y, Gao J, Wei C, Li J, Fang J, Li J, Fan JG, Song BL, Li Y*. Post-translational regulation of lipogenesis via AMPK-dependent phosphorylation of insulin-induced gene. Nature Communications 2019;10(1):623
9. Zhang F, Hu Z, Li G, Huo S, Ma F, Cui A, Xue Y, Han Y, Gong Q, Gao J, Bian H, Meng Z, Wu H, Long G, Tan Y, Zhang Y, Lin X, Gao X, Xu A, Li Y*. Hepatic CREBZF couples insulin to lipogenesis by inhibiting Insig activity and contributes to hepatic steatosis in diet-induced insulin-resistant mice. Hepatology 2018;68(4):1361-1375
10. Gong Q, Hu Z, Zhang F, Cui A, Chen X, Jiang H, Gao J, Chen X, Han Y, Liang Q, Ye D, Shi L, Chin YE, Wang Y, Xiao H, Guo F, Liu Y, Zang M, Xu A, Li Y*. Fibroblast growth factor 21 improves hepatic insulin sensitivity by inhibiting mammalian target of rapamycin complex 1. Hepatology 2016;64(2):425-438
11. Li Y*, Wong K, Giles A, Jiang J, Lee JW, Adams AC, Kharitonenkov A, Yang Q, Gao B, Guarente L, Zang M*. Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21. Gastroenterology 2014;146:539-549
12. Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E, Shyy JJ, Gao B, Wierzbicki M, Verbeuren TJ, Shaw RJ, Cohen RA, Zang M*. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metabolism 2011;13:376-388